3D printed PLGA implants: How the filling density affects drug release.

Different types of ibuprofen-loaded, poly (D,L lactic-co-glycolic acid) (PLGA)-based implants were prepared by 3D printing (Droplet Deposition Modeling). The theoretical filling density of the mesh-shaped implants was varied from 10 to 100%. Drug release was measured in agarose gels and in well agitated phosphate buffer pH 7.4. The key properties of the implants (and dynamic changes thereof upon exposure to the release media) were monitored using gravimetric measurements, optical microscopy, Differential Scanning Calorimetry, Gel Permeation Chromatography, and Scanning Electron Microscopy. Interestingly, drug release was similar for implants with 10 and 30% filling density, irrespective of the experimental set-up. In contrast, implants with 100% filling density showed slower release kinetics, and the shape of the release curve was altered in agarose gels. These observations could be explained by the existence (or absence) of a continuous aqueous phase between the polymeric filaments and the "orchestrating role" of substantial system swelling for the control of drug release. At lower filling densities, it is sufficient for the drug to be released from a single filament. In contrast, at high filling densities, the ensemble of filaments acts as a much larger (more or less homogeneous) polymeric matrix, and the average diffusion pathway to be overcome by the drug is much longer. Agarose gel (mimicking living tissue) hinders substantial PLGA swelling and delays the onset of the final rapid drug release phase. This improved mechanistic understanding of the control of drug release from PLGA-based 3D printed implants can help to facilitate the optimization of this type of advanced drug delivery systems.

3D printed PLGA implants: APF DDM vs. FDM.

3D Printing offers a considerable potential for personalized medicines. This is especially true for customized biodegradable implants, matching the specific needs of each patient. Poly(lactic-co-glycolic acid) (PLGA) is frequently used as matrix former in biodegradable implants. However, yet relatively little is known on the technologies, which can be used for the 3D printing of PLGA implants. The aim of this study was to compare: (i) Arburg Plastic Freeforming Droplet Deposition Modeling (APF DDM), and (ii) Fused Deposition Modeling (FDM) to print mesh-shaped, ibuprofen-loaded PLGA implants. During APF DDM, individual drug-polymer droplets are deposited, fusing together to form filaments, which build up the implants. During FDM, continuous drug-polymer filaments are deposited to form the meshes. The implants were thoroughly characterized before and after exposure to phosphate buffer pH 7.4 using optical and scanning electron microscopy, GPC, DSC, drug release measurements and monitoring dynamic changes in the systems' dry & wet mass and pH of the bulk fluid. Interestingly, the mesh structures were significantly different, although the device design (composition & theoretical geometry) were the same. This could be explained by the fact that the deposition of individual droplets during APF DDM led to curved and rather thick filaments, resulting in a much lower mesh porosity. In contrast, FDM printing generated straight and thinner filaments: The open spaces between them were much larger and allowed convective mass transport during drug release. Consequently, most of the drug was already released after 4 d, when substantial PLGA set on. In the case of APF DDM printed implants, most of the drug was still entrapped at that time point and substantial polymer swelling transformed the meshes into more or less continuous PLGA gels. Hence, the diffusion pathways became much longer and ibuprofen release was controlled over 2 weeks.

Development of nanofibrillar morphologies in poly(l-lactide)/poly(amide) blends: role of the matrix elasticity and identification of the critical shear rate for the nodular/fibrillar transition.

Bio-based poly(l-lactide)/poly(amide-11) blends (PLA/PA11, 80/20 w/w) and poly(l-lactide)/poly(amide-6) blends (PLA/PA6, 80/20 w/w) are processed by twin-screw extrusion followed by injection-moulding and key rheological parameters controlling their morphologie are investigated. The same work is done using the same PLA modified by a multi-step reactive extrusion route with an epoxy-based chain extender to obtain modified poly(lactide)/poly(amide-11) (PLA-j/PA11 80/20 w/w) blends. The morphologies of the extruded materials and of the injection moulded parts are characterized by SEM and their formation is deeply discussed via rheological investigation to highlight the contribution of viscosity, elasticity and interfacial tension. The existence of a critical shear rate related to the transition from nodular to fibrillar morphology is highlighted and the results are in good agreement with the condition of fibrillation Ca/Ca(crit) ≥ 4. Interestingly, with the exception of PLA/PA6 specimens, all blends obviously display uniform thin-thread fibrillar morphologies after injection-moulding. Compared with pure PLA, a drastic increase of the ductility was observed in the blends exhibiting a fiberlike structure without meanwhile sacrificing the stiffness. This study confirms that, through the appropriate choice of blend components (viscosity and elasticity ratio, flow conditions, interfacial tensions) the in situ fibrillation concept provides access, at a reasonable cost, to new materials with improved thermomechanical performances, without sacrificing weight and ability to be recycled.

Structure-barrier property relationship of biodegradable poly(butylene succinate) and poly[(butylene succinate)-co-(butylene adipate)] nanocomposites: influence of the rigid amorphous fraction.

Composites composed of polyesters, poly(butylene succinate) (PBS) or poly[(butylene succinate)-co-(butylene adipate)] (PBSA), and 5 wt% of montmorillonite (CNa) or organo-modified montmorillonite (C30B) were melt-processed and transformed into films by either compression-molding or extrusion-calendering. XRD, rheological measurements and TEM images clearly indicated that films containing CNa are microcomposites, while nanocomposites were observed for those containing C30B. Using Flash DSC, it was possible, for the first time, not only to measure the heat capacity step at the glass transition of these two materials in their amorphous state, but also to investigate whether the preparation technique influenced the Rigid Amorphous Fraction (RAF) in our PBS- and PBSA-based nanocomposites. In this work, we have successfully shown the correlation between the microstructure of the films and their barrier properties, and especially the role played by the RAF. Indeed, the lowest permeabilities to gases and to water were determined in the films containing the highest RAF in both PBS- and PBSA-based materials.

Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) based nanocomposites: influence of the microstructure on the barrier properties.

Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB-co-4HB) films containing various contents of organo-modified montmorillonite C30B nanoclays were prepared by melt intercalation. Wide angle X-ray diffraction measurements and transmission electron microscopy observations evidenced aggregated and intercalated structures with individual nanoclay platelets in the nanocomposites and an orientation of nanoclays. Differential scanning calorimetry measurements showed that the nanoclay did not influence the crystalline structure of the matrix because it is mainly located in the polymer amorphous phase. The influence of the filler on the barrier properties of the film was evaluated by water diffusion, gas permeation (CO2, N2, O2) and liquid water sorption measurements. A decrease of the N2 permeability was measured due to the tortuosity effect of the filler associated with a decrease of the solubility within the matrix. The influence of the filler was more marked for O2 due to the larger decrease of O2 solubility. In contrast, the CO2 permeability increased whatever the filler content because of a facilitated transport mechanism due induced by the presence of quaternary ammonium cations on the C30B surface. The decrease of the water permeability with the filler was explained by a competition between the kinetic (diffusivity) and thermodynamic (solubility) contributions defining the permeability process.

Studies on the effect of storage time and plasticizers on the structural variations in thermoplastic starch.

Starch was combined with plasticizers such as glycerol, sorbitol, glycerol/sorbitol and urea/ethanolamine blends by means of high shear extrusion process to prepare thermoplastic starch (TPS). Effect of storage time and plasticizers on the structural stability of melt processed TPS was investigated. Morphological observation, X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy reveal that melt extrusion process is efficient in transforming granular starch into a plasticized starch for all plasticizer compositions. XRD analysis highlights major changes in the microstructure of plasticized starch, and dependence of crystalline type and degree of crystallinity mainly on the plasticizer composition and storage time. Dynamical mechanical analysis (DMA) yields a decrease of the peak intensity of loss factor with aging time. The effect of ageing on tensile strength also appears to be highly dependent on the plasticizer composition. Thus, through different plasticizer combinations and ageing, starch-based materials with significant differences in tensile properties can be obtained, which may be tuned to meet the requirements of a wide range of applications.

Deformation mechanisms of plasticized starch materials.

The aim of this paper is to understand the influence of plasticizer and plasticizer amount on the mechanical and deformation behaviors of plasticized starch. Glycerol, sorbitol and mannitol have been used as plasticizers. After extrusion of the various samples, dynamic mechanical analyses and video-controlled tensile tests have been performed. It was found that the nature of plasticizer, its amount as well as the aging of the material has an impact on the involved deformation mechanism. The variations of volume deformation could be explained by an antiplasticization effect (low plasticizer amount), a phase-separation phenomenon (excess of plasticizer) and/or by the retrogradation of starch.

Preparation and properties of novel melt-blended halloysite nanotubes/wheat starch nanocomposites.

Novel bionanocomposites based on halloysite nanotubes as nanofillers and plasticized starch as polymeric matrix were successfully prepared by melt-extrusion for the first time. Both modified and non modified halloysites were added at different weight contents. The structural, morphological, thermal and mechanical properties of plasticized starch/halloysites nanocomposites were investigated. Melt-compounding appears to be a suitable process to uniformly disperse nanotubes in the plasticized starch matrix. Interactions between plasticized starch and halloysites in the nanocomposites and microstructure modifications were monitored using Fourier transfer infrared spectroscopy, X-ray diffraction and dynamic mechanical analysis. Addition of halloysite nanotubes slightly enhances the thermal stability of starch (onset temperature of degradation delayed to higher temperatures). The tensile mechanical properties of starch are also significantly improved (up to +144% for Young's modulus and up to +29% for strength) upon addition of both modified and unmodified halloysites, interestingly without loss of ductility. Modified halloysites lead to significantly higher Young's modulus than unmodified halloysites.